Understanding breast cancer

By Marc Ramirez; Seattle Times Staff Reporter
Copyright 1998 Seattle Times
September 9, 1998

It is the second-highest cause of cancer-related deaths for women in the United States, after lung cancer. One in nine women will develop it in their lifetimes. Fortunately, the majority will survive. Two new ways of fighting breast cancer are closer to reality for thousands of U.S. women.

Recently recommended by advisers to the Food and Drug Administration, both are systemic treatments that recognize that the entire body has or could become the stage in a woman's war against breast cancer and thus deploy their weaponry throughout.

Local treatment, on the other hand, includes surgery and radiation, focusing attention on the area where the tumor was discovered.

Systemic treatment, which includes chemotherapy, hormone therapy, immunotherapy and gene therapy, is the focus of most research, and advances have escalated in the past five years. Most recently:

In April, a North American study showed the drug tamoxifen could reduce breast-cancer incidence by 45 percent in otherwise healthy, high-risk patients. On Sept. 2, despite possible serious side effects and European studies contradicting those findings, the FDA advisory panel cautiously recommended its use for those patients.

Tamoxifen already is used as a standard treatment to help treat or prevent recurrences. But it has rare but serious side effects such as uterine cancer and blood clots.

This fall, Seattle will be a test site for tamoxifen and another promising drug, raloxifene, which both act as anti-estrogens on breast tissue, reducing the chances that breast cells will multiply and become cancerous.

Raloxifene, a treatment for thinning bones caused by osteoporosis, has been shown to cut breast-cancer risk more than 60 percent. But long-term effects remain unknown.

Both will most likely benefit women in whom cancer-cell growth is stimulated by the hormones estrogen or progesterone.

Last week, the FDA panel recommended approval of the drug Herceptin, which marks an advance on a different front entirely - immunotherapy. Most forms of this treatment currently are experimental, but involve using the immune system to fight cancer.

Herceptin is an antibody that inhibits a protein produced by the gene HER2 / neu, whose overpopulation, linked to one-third of breast-cancer cases, aids spread of the disease and reduces chemotherapy's effectiveness. Studies have shown Herceptin shrinks tumors and prolongs life by an average of three months.

Studies to determine Herceptin's usefulness for women in earlier stages of cancer will likely begin by year's end, says oncologist Julie Gralow of the University of Washington's School of Medicine.

In addition, UW oncologists Nora Disis and Martin Cheever are among those working on "vaccines" to trick the body into recognizing such mutations as foreign, but results are several years away.

"Hopefully someday we'll be able to get rid of chemotherapy entirely," Gralow says.

Another systemic treatment is a class of nontoxic drugs called biphosphonates, which fight bone loss.

One, pamidronate, is already given to women whose breast cancer has spread to their bone marrow. A study reported earlier this month showed a second biphosphonate, clodronate, reduced deaths among breast-cancer patients by two-thirds when combined with standard treatment.

A third, zoledranate, will be studied beginning this fall in a national, multi-clinic study coordinated by Gralow.

Women interested in participating in the studies can call 206-667-6544 for the taxomifen / raloxifene study, 206-548-7959 for the zoledranate study or 206-616-9538 for the breast-cancer vaccine study. ------------------------------- How breast cancer develops Breast are made up of fatty tissue surrounding lobules that produce milk and ducts that channel the milk to the nipples. Breast cancer begins in the ducts or lobules, first appearing as a small group of abnormal cells. If untreated, the cancerous cells keep growing until they spread to the body'a lymph system, through which they will eventually spread to other organs in the body.
Stages of breast cancer

A health duct is a tube lined with normal cells, and is unblocked. An overgrowth of normal cells, which may begin to block the duct, is called hyperplasia. Some of these cells might begin to appear abnormal.
- Stage 0:

In stu carcinomas are confined to the duct. They may be detected by a mammogram but rarely cause a noticeable lump.
Stage 1:

Lump develop when abnormal cells escape the ducts or lobules and invade adjoining tissue. In Stage 1 cancer, the tumor is still less than about three-quarters of an inc. There is no lymph-node involvement.
Stage 2:

Tumor is 1-2 inches in diameter now, and cancer may be spreading to lymph nodes around the breast and in the shoulder.
Stage 3:

Tumor is larger than 2 inches and may have invaded the chest wall or skin; cancer has spread to lymph nodes.
Stage 4:

Cancer has metastasized meaning it has spread to distant sites, such as lungs, bone or live.
Who is at risk

The highest risk factors for breast cancer are simply being a woman and getting older. According to the University of Washington Medical Center, the average age of a woman diagnosed with the disease is 62. And about three of every four women diagnosed are 50 or older. An estimated 179,300 women will contract breast cancer this year; another 43,500 will die. (The disease also afflicts a small number of men: 1,600 men will develop it and 400 will die.) The 20-year death rate is down slightly, probably because of early detection and improved treatment.
Known risk factors

About 70 percent of women diagnosed with breast cancer have no identifiable risk factors. But women with the following conditions are at increased risk: -- Previous case of breast cancer, or certain benign breast problems. -- Close relative - particularly sister, mother or daughter - had breast cancer. Only 5 percent or 10 percent of cases are inherited. -- Childless or had first child after age 30 -- Menstruation began before age 12 or lasted after age 50.
Additional factors that some studies have shown to correlate with increase risk: -- Long-term or recent use of oral contraceptives. -- Weight gain or high-fat diet -- High alcohol intake (2 glasses or more of wine or hard liquor daily). -- Physical inactivity -- Pesticides or other chemical exposures.

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